title: Reduced numbers of cortical GABA-immunoreactive neurons in the chronic D-galactose treatment model of brain aging.
abstract: Chronic administration of d-galactose (d-gal) is widely used to mimic the process of brain aging; however, the neural mechanisms are still poorly understood. In this study, we investigated the effect of long-term d-gal treatment on the number of GABA-immunoreactive neurons in rat cerebral cortex and the behavioral correlates. After eight weeks of daily subcutaneous injection of d-gal (100mg/ml/kg), rats showed reduced exploratory activity and lower ambulation in the open field compared to controls. There was no significant reduction in total neurons in the cortex, but there was a marked decrease in the number of GABA-immunoreactive neurons in all cortical layers of d-gal-treated rats. The ratio of GABA-immunoreactive neurons to total neurons was significantly lower in all cortical layers of d-gal-treated rats, with greatest reductions in output layers III (39.9% reduction), V (46.3%), and VI (48.4%). Our study provides the first evidence that chronic d-gal treatment may decrease cortical GABAergic neurotransmission, especially in cerebral output layers. The reduction in GABA-immunoreactive cell number likely disrupts the intracortical excitatory/inhibitory balance and may contribute to the behavioral deficits observed in this aging model.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, China.
authors.forename: Xiaosu
authors.initials: X
authors.lastname: Gu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Hu
authors.forename: Qin
authors.initials: Q
authors.lastname: Gu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wu
authors.forename: Maohong
authors.initials: M
authors.lastname: Cao
authors.forename: Kaifu
authors.initials: K
authors.lastname: Ke
authors.forename: Chunfeng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects*; D005690:Galactose / Q000008:administration & dosage*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005690:Galactose
keywords: Cerebral cortex; Rat; d-Galactose; γ-Aminobutyric acid